Evidence map›Paper›PMID 25788712›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2015

Inhibition of extracellular cyclophilins with cyclosporine analog and development of atherosclerosis in apolipoprotein E-deficient mice.

Michael Ditiatkovski, Vijaya N L V Neelisetti, Huanhuan L Cui, Miroslav Malesevic, Gunter Fischer, Michael Bukrinsky, Dmitri Sviridov

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of pharmacology and experimental therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.5field-weighted citation impact, top 34% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Macrophage lipid accumulation in the presence of immunosuppressive drugs mycophenolate mofetil and cyclosporin A.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2019
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 3 countries.

Michael DitiatkovskiBaker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia (M.D., V.N.L.V.N., H.L.C., D.S.); Department of Biochemistry, Martin Luther University of Halle-Wittenberg, Halle (Saale), Germany (M.M.); Max Planck Institute for Biophysical Chemistry, Gottingen, Germany (G.F.); and Department of Microbiology, and Immunology and Tropical Medicine, George Washington University, Washington, DC (M.B.).
Vijaya N L V NeelisettiBaker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia (M.D., V.N.L.V.N., H.L.C., D.S.); Department of Biochemistry, Martin Luther University of Halle-Wittenberg, Halle (Saale), Germany (M.M.); Max Planck Institute for Biophysical Chemistry, Gottingen, Germany (G.F.); and Department of Microbiology, and Immunology and Tropical Medicine, George Washington University, Washington, DC (M.B.).
Huanhuan L CuiBaker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia (M.D., V.N.L.V.N., H.L.C., D.S.); Department of Biochemistry, Martin Luther University of Halle-Wittenberg, Halle (Saale), Germany (M.M.); Max Planck Institute for Biophysical Chemistry, Gottingen, Germany (G.F.); and Department of Microbiology, and Immunology and Tropical Medicine, George Washington University, Washington, DC (M.B.).
Miroslav MalesevicBaker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia (M.D., V.N.L.V.N., H.L.C., D.S.); Department of Biochemistry, Martin Luther University of Halle-Wittenberg, Halle (Saale), Germany (M.M.); Max Planck Institute for Biophysical Chemistry, Gottingen, Germany (G.F.); and Department of Microbiology, and Immunology and Tropical Medicine, George Washington University, Washington, DC (M.B.).
Gunter FischerBaker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia (M.D., V.N.L.V.N., H.L.C., D.S.); Department of Biochemistry, Martin Luther University of Halle-Wittenberg, Halle (Saale), Germany (M.M.); Max Planck Institute for Biophysical Chemistry, Gottingen, Germany (G.F.); and Department of Microbiology, and Immunology and Tropical Medicine, George Washington University, Washington, DC (M.B.).
Michael BukrinskyBaker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia (M.D., V.N.L.V.N., H.L.C., D.S.); Department of Biochemistry, Martin Luther University of Halle-Wittenberg, Halle (Saale), Germany (M.M.); Max Planck Institute for Biophysical Chemistry, Gottingen, Germany (G.F.); and Department of Microbiology, and Immunology and Tropical Medicine, George Washington University, Washington, DC (M.B.).
Dmitri SviridovBaker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia (M.D., V.N.L.V.N., H.L.C., D.S.); Department of Biochemistry, Martin Luther University of Halle-Wittenberg, Halle (Saale), Germany (M.M.); Max Planck Institute for Biophysical Chemistry, Gottingen, Germany (G.F.); and Department of Microbiology, and Immunology and Tropical Medicine, George Washington University, Washington, DC (M.B.) Dmitri.Sviridov@bakeridi.edu.au.
Martin Luther University Halle-Wittenberg · DEGeorge Washington University · USMax Planck Institute for Biophysical Chemistry · DE

Funding

The District of Columbia Developmental Center for AIDS Research (DC D-CFAR)P30AI087714 · NIAID · GEORGE WASHINGTON UNIVERSITY · PI GREENBERG, ALAN EDWARD · 2010 to 2014
$8.4M
HIV Disease and Impairement of High Density Lipoprotein MetabolismR01HL101274 · NHLBI · GEORGE WASHINGTON UNIVERSITY · PI BUKRINSKY, MICHAEL ILYA, FITZGERALD, MICHAEL LEO · 2010 to 2015
$4.0M
Mechanisms of virus-induced impairment of reverse cholesterol transportR01HL093818 · NHLBI · GEORGE WASHINGTON UNIVERSITY · PI BUKRINSKY, MICHAEL ILYA, SVIRIDOV, DMITRI · 2009 to 2013
$1.6M
NHLBI NIH HHS R01 HL093818NHLBI NIH HHS R01 HL101274NIAID NIH HHS P30 AI087714
6 · The paper itself

Abstract

Cyclophilins exert both intracellular and extracellular activities related to immune responses and inflammation, which have been implicated in pathogenesis of atherosclerosis. Pan-inhibition of cyclophilins has both pro- and antiatherosclerotic properties, but specific contributions of extracellular and intracellular cyclophilins to these effects have not been characterized. Here, using selective inhibitor of extracellular cyclophilins, we investigated the role of these molecules in atherosclerosis. Apolipoprotein E-null mice fed a high-fat diet received intraperitoneal injections every second day of either vehicle or two analogs of cyclosporine A (CsA): [Melle](4)-CsA (NIM811), a nonimmunosupressive cell-permeable inhibitor of both intracellular and extracellular cyclophilins; and [(4R)-4-[(6-carboxy-1H-benzo[d]imidazol-2-yl)-methyl]-4-methyl-l-threonine](1)-CsA (MM284), cell-impermeable analog only inhibiting extracellular cyclophilins. Development of atherosclerosis and composition of plaques in aorta and innominate artery were studied. Both analogs increased abundance and cross-sectional size of the atherosclerotic plaques in aorta but did not affect development of atherosclerosis in innominate artery. Neither compound affected abundance of macrophages and amount of vascular cell adhesion molecule-1 or nitrotyrosine in the plaques of both arteries. Both compounds reduced the amount of collagen in innominate artery without affecting abundance of collagen in aortic sinus. MM284, but not NIM811, significantly reduced plasma concentration of tumor necrosis factor-α (TNFα); neither compound affected plasma concentrations of interleukin (IL)-6, IL-10 or monocyte chemoattractant protein-1. Ratio between different populations of immune cells in blood or isolated from lymph nodes and spleen as well as plasma lipoprotein profile were unaffected by both compounds. In conclusion, selective inhibition of extracellular cyclophilins reduced TNFα levels in plasma but increased atherosclerosis.

Indexed as

AnimalsApolipoproteins EAtherosclerosisCross-Sectional StudiesCyclophilinsCyclosporinsCytokinesImmunosuppressive AgentsLipoproteinsMaleMiceMice, KnockoutPlaque, AtheroscleroticApolipoproteins ECyclophilinscyclosporine A, 4-((6-carboxy-1H-benzo(d)imidazol-2-yl)methyl)-4-methylthreonine)(1)-CyclosporinsCytokinesImmunosuppressive AgentsLipoproteins

Identifiers

PMID25788712
PMCPMC11047113
OpenAlexW2152311731

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.